The primary goal of this group is to identify new agents of potential clinical use in treating solid tumors. A major effort over the past 5 years has been the use of an in vitro assay which may be helpful as a preclinical screening model for antitumor agents. The model has been used to predict the clinical activity of 7 chemotherapeutic agents against 11 human colorectal carcinoma cell lines which have been developed in this branch. Using the model, we have shown that leucovorin enhances the in vitro cytotoxicity of the fluoropyridines versus our panel of colorectal cell lines. A study was also performed to detect possible synergy between etoposide and cisplatin in a panel of 8 human bronchogenic carcinoma cell lines. Extensive analysis revealed no in vitro synergy, a finding at variance with standard feeling. Schedule dependent drug interaction has been documented between methotrexate and 5-fluorouracil. Persantine has been shown to enhance the cytotoxicity of 10-EDAM in human lung cancer cell lines. Clinical trials are planned to explore this. At present, we are involved in several trials of new experimental therapeutic agents: a radiolabeled monoclonal antibody 90yttrium-T101) in mycosis fungoides and chronic lymphocytic leukemia; 4-ipomeanol in lung cancer. A phase I trial of hepsulfam has recently been completed, and maximally tolerated schedule identified as 360 mg/m2 i.v. every 5 weeks. Dose limiting toxicity was leukopenia.